Combi-TED: A multicenter, phase II, open-label, randomized trial evaluating efficacy of OSE2021 plus docetaxel or OSE2021 plus nivolumab as second-line therapy in metastatic NSCLC progressing after first-line chemo-immunotherapy.
Authors: Federico Cappuzzo, Giulia Pasello, Angelo Delmonte, Lorenza Landi, Beatrice Benetti, Giulio Metro, Mario Rosario D'Andrea, Stefania Gori, Gloria Borra, Francesca Mazzoni, Claudio Verusio, Maria Pagano, Diana Giannarelli, Andrea Vincent Bonetti, Michele Maio, Antonino Scimone, Vincenzo Adamo
Journal: Journal of Clinical Oncology (2022)

TPS9140 Background: First line combination of chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) compared with chemotherapy alone in non-small cell lung cancer (NSCLC) patients. However, only few options are available at chemoimmunotherapy failure, with docetaxel representing the standard of care. Tedopi is a cancer vaccine which stimulates killer T cells, currently under development for the therapy of HLA-A2+ lung cancer. In the ATALANTE-1 Phase III trial (EudraCT no. 2015-003183-36), Tedopi provided clinical benefits in patients with advanced NSCLC who failed to respond to checkpoint inhibitors. Given the need for new therapeutic options in patients failing first-line chemo-immunotherapy and the encouraging preliminary data with Tedopi, there is a strong rationale for investigating the activity of Tedopi plus nivolumab or Tedopi plus docetaxel in patients with metastatic NSCLC failing standard first-line therapy. Methods: This is a phase II, non-comparative, randomized multicenter study assessing the combination of Tedopi with docetaxel or nivolumab in NSCLC patients failing after first-line chemoimmunotherapy (EudraCT no. 2020-005170-10). All NSCLC patient candidates for second-line therapy are considered eligible for the study if they are HLA-A2+, with no evidence of EGFR mutations or ALK/ROS1 rearrangement and if they progressed after at least 4 cycles of previous first-line chemo-immunotherapy. Patients are randomly assigned to Tedopi plus docetaxel, Tedopi plus nivolumab (treatment arms) or docetaxel monotherapy (standard arm). The primary endpoint is 1-year OS rate. Secondary endpoints include OS, 2-year OS rate, progression-free survival (PFS), objective response rate (ORR), and safety. An explorative analysis of the correlation of efficacy with several tumor or blood biomarkers (PD-L1 expression, tumor mutational burden, Tedopi neoantigen expression, T cell infiltration), is also performed. Sample size was calculated assuming a 1-year OS rate in the standard arm of 20%. According to the single-stage design, in both treatment arms a 1-year OS rate of 20% would imply that treatment does not warrant further investigation and a 1-year OS rate of 40%, would imply that treatment has a sufficient activity. With a one-sided significance level of 5% and a power of 80%, a total number of 105 patients (35 per treatment arm) need to be enrolled. At the drafting of this abstract, 7 patients have already been enrolled. Total follow-up will be 24 months from last enrolment, for an approximate duration of 48 months. Clinical trial information: NCT04884282.